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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Pharmacological reactivation of p53 in the era of precision anticancer medicine

Amos Tuval1, Charlotte Strandgren1, Angelos Heldin1

  • 1Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden.

Nature Reviews. Clinical Oncology
|December 15, 2023
PubMed

Insights

Targeting the tumor suppressor p53 (encoded by TP53) offers new cancer therapy potential. Researchers are exploring compounds to restore p53 function in wild-type and mutant cancers, facing challenges in clinical application.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • The TP53 gene, frequently mutated in cancer, encodes the p53 tumor suppressor protein, a key target for novel cancer therapies.
  • Current strategies aim to enhance wild-type p53 activity or restore function in p53 mutants, with compounds targeting p53-MDM2 interactions or mutant p53 refolding/readthrough.

Purpose of the Study:

  • To review the current landscape of p53-targeting cancer therapies.
  • To discuss the biological complexities and challenges influencing the clinical efficacy of these agents.
  • To propose strategies for improving the therapeutic outcomes of p53-restoring drugs.

Main Methods:

  • Review of existing literature on p53 biology and therapeutic strategies.
  • Analysis of factors influencing p53 activity in different cellular and microenvironmental contexts.
  • Discussion of clinical trial data and reasons for variable efficacy.

Main Results:

  • Several p53-targeting compounds are under investigation, with some in clinical trials for various cancers.
  • No p53-targeting drug has yet received regulatory approval for clinical use.
  • Variable clinical activity of p53-restoring therapies is linked to complex interactions of p53 with its cellular and microenvironmental context.

Conclusions:

  • Despite significant progress, p53-targeting therapies face challenges that limit their clinical success.
  • A deeper understanding of p53 biology and its context-dependent functions is crucial for optimizing therapeutic strategies.
  • Future efforts should focus on personalized approaches and combination therapies to enhance the efficacy of p53-restoring agents.

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